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P059. Importance of NOD2 on mRNA and miRNA signatures in monocytes from Crohn's disease

M. Salem1, Y. Chen2, J.B. Seidelin1, A. Sandelin2, O.H. Nielsen1, 1Herlev University Hospital, Department of Gastroenterology, Herlev, Denmark, 2The Bioinformatics Centre, Department of Biology and Biotech Research and Innovation Centre, Copenhagen, Denmark


Nucleotide oligomerization domain 2 (NOD2) is an important component of the innate intercellular pathogen recognition system. Genetic variations in NOD2 are associated with severity of Crohn's disease (CD) and alterations of immunological responses. Several studies have demonstrated the relevance of regulation of messenger RNA (mRNA) by noncoding micro-RNA (miRNA) for a broad range of cellular mechanisms. Here the effect of NOD2 variations on mRNA and miRNA expression in human monocytes upon stimulation with the NOD2-specefic agonist, muramyl dipeptid (MDP) was investigated.


Monocytes were isolated using magnetic beads from peripheral blood mononuclear cells of 7 individuals with wild type (WT) healthy controls, WT CD patients, and NOD2-mutated CD patients, respectively. Next generation RNA sequencing was subsequently used to compare the total expression of both mRNA and miRNA before and after a challenge with MDP.


In particular the miRNA profiles seem to distinguish the difference between patients (Figs. 1A and 1B). Interestingly, the miRNA expression profiles of controls are more similar to NOD2-mutated CD patients. In addition, mRNA expressions might differentiate patients based on the difference before and after MDP (Figs. 1C and 1D). Remarkably, the gene expression of several important inflammatory components such as chemokines (i.e. CCL2, CCL4, CCL4L1, CCL8, CCL22, CXCL10, and CXCL11) was significantly lower in both WT and NOD2-mutated CD.

Figure 1. Heat maps of differentially expressed miRNA and mRNA. (A) miRNA before MDP, (B) miRNA after MDP, (C) mRNA before MDP, and (D) mRNA after MDP. Gene expression: blue = low and red = high.


Our findings shed light on the epigenetic influence of NOD2 in the total expression of mRNA and miRNA in CD. Thus, the expression signature of miRNA distinguishes patient groups whereas the mRNA profile distinguishes inflammatory states. Further, the mRNA expression of several important inflammatory contributors is affected indicating a crucial role of NOD2 in the pathogenesis of CD regardless of NOD2 genotype.